Response to Comment on Lachin et al. Association of Estimated Time-in-Range Capillary Glucose Levels Versus HbA_1c With Progression of Microvascular Complications in the Diabetes Control and Complications Trial. Diabetes Care 2022;45:2445–2448

We appreciate the opportunity to address the further comments from Drs. Ceriello and Prattichizzo (1) on our article (2). First, while further exploration of the relative contributions of the HbA_1c and time-in-range (TIR) would be of interest, as stated in the introduction of our article, our intention was to replicate the analyses of Beck et al. (3), which were built on data derived from the Diabetes Control and Complications Trial (DCCT). Thus, we only presented analyses of outcomes that had been included in the article by Beck et al. Second, we agree that the estimated TIR based on the seven-point profiles collected repeatedly during DCCT are an imperfect representation of TIR. However, continuous glucose monitoring was unavailable during DCCT and the seven-point profiles were the only method available to estimate TIR. These data were selected by Beck et al., and, therefore, we performed our analyses with the data available. The fact that our estimated TIR is imperfect was stated in the discussion. We welcome investigators to replicate the DCCT using continuous glucose monitoring but think it unlikely that this will ever occur. Finally, we agree that analyses of glucose variability may provide additional insights into pathophysiology. However, our previous analyses of these DCCT data (4) have shown that measures of glycemic variability were not associated with other outcomes when accounting for the updated mean HbA_1c. We certainly agree that the various associations are multifaceted and that further analyses are needed.